11-27499376-G-A

Position:

• chr11-27499376-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_018362.4(LIN7C):​c.421C>T​(p.Leu141Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: LIN7C NM_018362.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.88

Genes affected

LIN7C (HGNC:17789): (lin-7 homolog C, crumbs cell polarity complex component) Enables L27 domain binding activity and cytoskeletal protein binding activity. Involved in morphogenesis of an epithelial sheet. Located in cell-cell junction; cytoplasm; and plasma membrane. Part of MPP7-DLG1-LIN7 complex. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
LIN7C	NM_018362.4	c.421C>T	p.Leu141Phe	missense_variant	4/5	ENST00000278193.7	NP_060832.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
LIN7C	ENST00000278193.7	c.421C>T	p.Leu141Phe	missense_variant	4/5	1	NM_018362.4	ENSP00000278193.2
LIN7C	ENST00000524596.1	c.349C>T	p.Leu117Phe	missense_variant	3/4	1		ENSP00000435353.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 24, 2024

The c.421C>T (p.L141F) alteration is located in exon 4 (coding exon 4) of the LIN7C gene. This alteration results from a C to T substitution at nucleotide position 421, causing the leucine (L) at amino acid position 141 to be replaced by a phenylalanine (F). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.91
BayesDel_addAF	Uncertain	0.14	D
BayesDel_noAF	Uncertain	-0.030
CADD	Pathogenic	26
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;T
Eigen	Uncertain	0.43
Eigen_PC	Uncertain	0.53
FATHMM_MKL	Uncertain	0.97	D
LIST_S2	Benign	0.84	T;T
M_CAP	Uncertain	0.092	D
MetaRNN	Uncertain	0.62	D;D
MetaSVM	Benign	-0.75	T
MutationAssessor	Pathogenic	3.3	M;.
PrimateAI	Pathogenic	0.85	D
PROVEAN	Uncertain	-2.5	D;D
REVEL	Uncertain	0.33
Sift	Uncertain	0.022	D;D
Sift4G	Uncertain	0.0090	D;D
Polyphen		0.064	B;B
Vest4		0.89
MVP		0.65
MPC		1.2
ClinPred		0.99	D
GERP RS		6.0
Varity_R		0.47
gMVP		0.67

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr11-27520923;